Sir Peter MacCallum Department of Oncology - Theses
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ItemReal-world Management and Outcomes for Anaplastic Lymphoma Kinase (ALK)- rearranged Advanced Non-small Cell Lung Cancer and Impact of COVID-19 on Cancer Service Delivery( 2023-09)This thesis is divided into two parts. Part 1 - Real-world Management and Outcomes for Anaplastic Lymphoma Kinase (ALK)-rearranged Advanced Non-small Cell Lung Cancer (ALK+ aNSCLC) ALK-rearrangements are found in 4% of Non-small cell lung cancers (NSCLC). Although this condition remains incurable, survival appears to be improving over time, with a multitude of selective oral tyrosine kinase inhibitors (ALK-inhibitors) now available and with many patients receiving multiple lines of therapy. Whilst next-generation ALK-inhibitors are standard of care in the first line, how to best sequence available therapies beyond this remains unclear. This thesis examines outcomes for real-world patients with ALK+ aNSCLC, using cohorts from AURORA (Australia) and Flatiron health (United States). Key findings: median overall survival (mOS) of 84 months in the AURORA cohort (n=171) and 37 months in the Flatiron cohort (n=737). Positive prognostic factors: never-smoking history, treatment in an academic setting and initial early stage at diagnosis. Gender was not prognostic. Treatment patterns varied and changed over time. Initial treatment with 2nd generation ALK-inhibitor was associated with improved survival over chemotherapy; initial treatment with 1st generation ALK-inhibitor followed by 2nd generation ALK-inhibitor was associated with improved survival compared to initial chemotherapy followed by 1st generation ALK-inhibitor. These retrospective observational studies represent the largest for people with ALK+ aNSCLC in Australia (AURORA) and globally (Flatiron). Future research may focus on intensifying treatment for people with a smoking history. Further work is required to determine why treatment in a community setting correlated with poorer survival in the US. Identifying optimal treatment sequences will require larger contemporary patient databases; collaboration is required among research organisations and with pharmaceutical companies conducting post-marketing studies. Part 2 - Impact of COVID-19 on Cancer Service Delivery Amid the early stages of the COVID-19 pandemic, significant shifts in patient presentation and oncology health service provision for people with lung and other cancer-types were observed globally. This research aimed to obtain timely real-world data on how clinicians perceived alterations in cancer service delivery due to COVID-19. Surveys were distributed to oncology clinicians through international professional societies in 2020. Clinicians highlighted substantial changes in oncology services. In the early period (May-June 2020), 89% of clinicians reported altering their practice due to COVID-19; including being less likely to initiate and more likely to cease systemic therapy in palliative and curative settings. Telehealth use was rapidly expanded; many clinicians reported concerns that this may negatively impact patient outcomes. Clinicians reported seeing fewer new patients in clinic. In the later period (October-November 2020), clinicians reported more advanced disease presentations and a swing back towards pre-COVID practice. Clinicians’ reported concerns regarding potential negative impact on cancer-related outcomes are further substantiated by global reports of fewer cancer diagnoses across 2020 and modelling studies predicting increase cancer-related mortality and health-care costs due to such changes. For cancer-related outcomes to be optimised through future pandemic events, heath-systems and policy makers need to have implementable action plans to rapidly upscale mitigation strategies, such as public education campaigns, telehealth and hospital in the home.